Open-laBel Dose-escalation Study for CRISPR/cas13- Rna TargetInG THerapy for the Treatment of Neovascular Age-related Macular Degeneration in Phase I Trial

Age-related macular degeneration (AMD) leads to severe and irreversible vision loss, while neovascular AMD (nAMD) accounts for 80-90% of AMD blindness. Current anti-VEGF therapies are the standard of care, but these therapies require life-long repeated intraocular injections. These frequent intravitreal injections increase the risk of complications, including submacular hemorrhage, intraocular hypertension, inflammation, and retinal detachment. Therefore, repeated treatments for nAMD place a substantial burden on healthcare systems, patients, and their caregivers. Additionally, approximately 25-35% of individuals with aggressive nAMD show suboptimal responses to the anti-VEGF therapies, experience treatment-extended failure, or require intensive, frequent intraocular injections, and do not prevent irreversible vision loss.

HG202 is a CRISPR/Cas13 RNA-editing therapy delivered through one single AAV vector to partially knock down the expression of VEGFA and thus inhibit CNV formation in AMD. The long-term, stable delivery of HG202 following a one-time gene-editing therapy treatment for nAMD may potentially reduce the frequent injections and the potential risks of currently available anti-VEGF therapies since it does not rely on the long-term expression of anti-VEGF antibodies.

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Key information

Conditions

Neovascular Age-related Macular Degeneration (nAMD) Eye Diseases Macular Degeneration Retinal Degeneration Retinal Diseases

Age range

50 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Males or females ≥ 50 and ≤ 85 years at the time of signing the ICF;
Active macular choroidal neovascularization (MNV) secondary to nAMD in the study eye;
Sentinel (1st) subject for each dose cohort must have a BCVA ≤ 20/63 and ≥ 20/400 (≤63 and ≥ 19 ETDRS letters) in the study eye. Following the sentinel subject evaluation, the rest of the subjects in the dose cohort must have a BCVA between ≤ 20/40 and ≥ 20/400 (≤ 73 and ≥ 19 ETDRS letters) in the study eye.
Able to perform visual acuity and retinal function tests and able and willing to comply with study procedures for this clinical trial.

Exclusion criteria

Retinal or subretinal hemorrhage, scarring, or fibrosis of greater than 50% of the total lesion in the study eye;
Other ocular diseases that may affect central vision in the study eye;
Any other cause of CNV than nAMD in the study eye
Uncontrolled glaucoma in the study eye;
History or presence of corneal transplant or corneal dystrophy in the study eye;
History of other intraocular surgery in the study eye within 3 months prior to baseline;
Prior gene therapy or oligonucleotide therapy;
Other conditions judged by the investigator as inappropriate for the study.

Treatment and study plan

HG202

Genetic

Method of Administration: Once unilateral subretinal injection; The duration of the study includes a 4-week screening period, enrollment visit, treatment visit and 52 weeks follow-up period, 4 more years long term follow up as an extension study.

Primary outcomes

Incidence and severity of ocular and systemic adverse events

Time frame: 52 weeks

Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)

Secondary outcomes

Mean change from baseline in best-corrected visual acuity (BCVA)

Time frame: 52 weeks

Change from baseline in BCVA as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) chart in the study eye at different doses
Mean change in annualized rate of supplemental injections

Time frame: 52 weeks

Change from baseline in the number of anti-VEGF injections which is annualized to a per year rate in the study eye at different doses

Study contacts

Contact information is provided by the study sponsor or research team.

Study Director

CONTACT

[email protected]

732-318-9873

Sponsors and collaborators

Lead sponsor

HuidaGene Therapeutics Co., Ltd.

Industry

Registry information

Official study title

A Phase 1, Open-label, Multiple-cohort, Dose-escalation Study to Evaluate the Safety and Tolerability of HG202 High-fidelity CRISPR-Cas13 (hfCas13Y) RNA-targeting Therapy for Neovascular Age-related Macular Degeneration (nAMD)

Acronym: BRIGHT

Important dates

Study start: 2025
Primary completion: 2027
Study completion: 2031
First posted: Oct 2, 2024
Registry last updated: Oct 2, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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